P789: ANALYSIS OF THE CLINICAL FEATURES, PROGNOSIS AND GENE MUTATIONS IN PRIMARY MYELODYSPLASTIC SYNDROME PATIENTS WITH MYELOFIBROSIS
Authors: G. Xu, S. Zhu, H. Tong
Journal: HemaSphere (2022)

Background: Bone marrow(BM) fibrosis in myelodysplastic syndrome (MDS-MF) is observed approximately in 10–50% of primary MDS patients in the previous reports. BM biopsy is essential for the diagnosis and evaluation of MDS-MF patients and they differ from MDS without MF in terms of clinical performance, prognosis and survival. Although MDS-MF is associated with an adverse prognosis in the view of most hematologists, MDS-MF is not independently listed as a subtype of MDS according to the 2016 World Health Organization classification, indicating the need for further investigation. In this study, we retrospectively analyzed 417 newly diagnosed primary MDS cases in our hospital and to compare the clinical characteristics, prognosis and gene mutations of the two group patients with or without myelofibrosis. Aims: This study aims to analyze the clinical features, prognosis and characteristics of the gene mutations of the primary myelodysplastic syndrome with myelofibrosis (MDS-MF) patients, ultimately to improve the cognition of MDS-MF. Methods: From January 1, 2013, to February 1, 2020, 417 newly diagnosed primary MDS patients in the first affiliated hospital of Zhejiang University with bone marrow (BM) biopsy examination were included. They were divided into two groups according to whether BM associated with fibrosis (2005 European Myelofibrosis Network criteria), the MDS-MF group(MF grades 1–3）and the MDS without MF group (MF grade 0）.The clinical features, prognosis and gene alterations were analyzed between the two groups retrospectively. Results: ① MF was confirmed in 46.3％ cases of all the MDS patients（193/417）, of which 66.3％（128/193）were MF-1, 25.9％（50/193）were MF-2 and 7.8% were MF-3 respectively. There is no statistically significant difference in the proportion of subtypes patients according to the 2016 who classification (P=0.342). ②Compared with those without MF, MDS-MF were significantly associated with worse OS(P=0.035) and worse PFS(p<0.001). Subgroup analysis showed that both OS and PFS of either the MDS-MF1-2 group or the MDS-MF 3 group were also significantly worse than those of the MDS without MF group（P＝0.013 and <0.001 respectively）. ③The clinical features of the two groups were statistically significant differences in the higher number of BM blast cell(P=0.006), higher prevalence of death (P=0.031), higher rate of Leukemic transformation (P<0.001), higher level of serum lactate dehydrogenase (LDH) (p<0.001), higher level of β2-microgram (p=0.003) and higher level of CRP in the peripheral blood (P=0.004) in the MDS-MF group than in the MF0 group. ④Among all the patients,337 were finished Next-generation-sequencing (NGS) test. Using the same panel analysis, U2AF1 gene mutation was more frequently in the MDS-MF compared with those patients without MF (P=0.027). There was totally 14.2% (48/417) patients with the mutation of U2AF1, of which 19.7%（29/147) in MDS-MF group and 10.0%（19/190) in MDS without MF group. There was significant difference concomitant with U2AF1 mutation between the two groups(P=0.038). Image:Summary/Conclusion: MDS-MF has unique laboratory and clinical characteristics. MF is an independent risk factor for shorter overall survival (OS) and worse progression-free survival (PFS) in primary MDS. Evaluation of MF is very significant for prognosis judgment in primary MDS. The U2AF1 mutation may be a biomarker related to the poor prognosis of MDS-MF. However, the mechanism of U2AF1 in MDS-MF patients needs to be further explored.